Maternal tobacco smoking in pregnancy and

Transcription

Maternal tobacco smoking and children’s symptoms of hyperactivity/inattention_5_3_2015
Maternal tobacco smoking in pregnancy and children’s socio-emotional development at age 5:
the EDEN mother-child birth cohort study.
Maria Melchior1,2, Robleh Hersi1,2, Judith van der Waerden1,2, Béatrice Larroque‡3,4, Marie-Josèphe
Saurel-Cubizolles3,4, Aude Chollet1,2, Cédric Galéra5,6 and the EDEN Mother–Child Cohort Study Group7
1
Inserm, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Department of Social
Epidemiology, F-75013, Paris, France
2 Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1136, Pierre Louis Institute of Epidemiology and
Public Health, Department of Social Epidemiology, F-75013, Paris, France
3 INSERM, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology
and Biostatistics (U1153), Paris-Descartes University, Paris, France
4 UPMC Univ Paris 06, UMR S 953, F-75005, Paris, France
5 Department of Child and Adolescent Psychiatry, Charles Perrens Hospital, University of Bordeaux,
Bordeaux, France;
6 INSERM U897, Center for Research in Epidemiology and Biostatistics, Prévention et Prise en Charge
des Traumatismes, Bordeaux, France
Corresponding author: Maria Melchior, Inserm, UMR_S 1136, Hôpital Paul Brousse, 16 avenue Paul
Vaillant Couturier, 94800 Villejuif, [email protected], +33(0)1 77 74 74 27.
No reprints used
Keywords : tobacco use, pregnancy, ADHD, cohort study
Word count: abstract: 249
text: 3082
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The EDEN Mother–Child Cohort Study Group: I. Annesi-Maesano, J. Botton, M.A. Charles, P. DargentMolina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, A. Forhan, X. Fritel, A.
Germa, V. Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque, N. Lelong, J. Lepeule, G. Magnin, L.
Marchand, C. Nabet, R. Slama, M.J. Saurel-Cubizolles, M. Schweitzer, O. Thiebaugeorge.
1
Abstract
Background: There is debate as to whether maternal tobacco use in pregnancy is related to offspring
behavior later on. We tested this association examining multiple aspects of children’s behavior at age
5 and accounting for parental smoking outside of pregnancy, as well as child and family
characteristics.
Methods: Data come from a prospective community based birth cohort study (EDEN; n=1,113
families in France followed since pregnancy in 2003-2005 until the child’s 5th birthday). Maternal
tobacco use in pregnancy was self-reported. Children’s socio-emotional development (emotional
symptoms, conduct problems, symptoms of hyperactivity/ inattention, peer relationship problems,
prosocial behavior) was assessed by mothers using the Strengths and Difficulties Questionnaire (SDQ)
at age 5 years. Logistic regression analyses controlled for Inverse Probability Weights (IPW) of
maternal tobacco use calculated based on study center, children’s characteristics (sex, premature
birth, low birth weight, breastfeeding), maternal characteristics (age at the child’s birth, psychological
difficulties and alcohol use in pregnancy, post-pregnancy depression, and smoking), paternal smoking
in and post pregnancy, parental educational attainment, family income, parental separation, and
maternal negative life events.
Results: Maternal smoking in pregnancy only predicted children’s high symptoms of
hyperactivity/inattention (sex and study-center adjusted ORs: maternal smoking in the 1st trimester:
1.95, 95% CI 1.13-3.38; maternal smoking throughout pregnancy: OR=2.11, 95% CI 1.36-3.27). In IPWcontrolled regression models, only children of mothers who smoked throughout pregnancy had
significantly elevated levels of hyperactivity/inattention (OR=2.20, 95% CI 1.21-4.00).
Conclusions: Maternal tobacco smoking in pregnancy may contribute directly or through epigenetic
mechanisms to children’s symptoms of hyperactivity/inattention.
Keywords: cigarette, ADHD symptoms, addiction, mental health
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Introduction
Maternal tobacco use in pregnancy can have negative effects on children’s birth characteristics and
perinatal health (ex. increased risk of low birth weight and prematurity) [1, 2]. Moreover, children
whose mothers smoke appear to have elevated levels of behavioral and substance-related problems
[3-6]. In particular, research has consistently shown high rates of symptoms of
hyperactivity/inattention and Attention Deficit and Hyperactivity Disorder (ADHD) [7-12]. The
question of whether this association is causal has been widely debated [8] and findings from
genetically informative studies suggest that this is probably not the case: rather, high levels of
hyperactivity/inattention in children of smoking mothers could reflect the intergenerational
transmission of a genetic vulnerability to behavioral difficulties or incomplete control for confounding
factors such as socioeconomic position [9, 11, 13].
Nonetheless, past research on this topic had several limitations. First, the extent of genetic
confounding is yet uncertain. Studies conducted among siblings discordant with regard to maternal
tobacco use show no effect of this exposure on children’s behavior [10, 13], however these results
could be biased due to sample selection and an uneven distribution of confounders across siblings
[14]. In twin studies, estimates of heritability could be inflated because of gene x environment
interactions that are not entirely taken into account. Moreover, if genetic vulnerability plays a key
role, one expects paternal tobacco smoking to be associated with children’s behavior; however this is
not always the case [4, 9, 11, 12, 15]. Additionally, the likelihood of symptoms of
hyperactivity/inattention in the offspring should only moderately vary with the timing of maternal
smoking (pre, during or post-pregnancy). Yet studies on this topic have reported elevated levels of
behavioral problems only in children exposed to tobacco smoking in utero, including in historical
times when maternal smoking in pregnancy was widespread [12]. Second, due to reliance on small
samples [7, 9], merged datasets [5, 10] or data from birth registers [10], prior studies have not always
accounted for all relevant covariates, particularly social and economic factors. Third, with rare
exceptions [15], the specificity of the association between maternal smoking in pregnancy and
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symptoms of hyperactivity/ inattention in the offspring has not been thoroughly studied [10].
Research primarily examined children’s conduct problems or overall behavior [4] while a systematic
comparison between different types of difficulties that children may experience could help make
inferences about underlying mechanisms.
In the present study, using data from the French EDEN mother-child birth cohort study, we
examine the hypothesis that maternal tobacco smoking in pregnancy is associated with children’s
behavior at age 5 years. To account for limitations of past research, we analyze the data: 1) using
negative controls (paternal smoking), 2) comparing different time periods of exposure to maternal
smoking (pre-, during and post-pregnancy), 3) comprehensively assessing children’s social and family
environment, 4) using inverse probability weights (IPWs) to account for covariates, and 5) studying
multiple aspects of children’s behavior.
Methods
Study population
The EDEN mother-child cohort study (‘Etude sur les Déterminants pré et postnatals précoces du
développement psychomoteur et de la santé de l’ENfant’) aims to examine pre- and postnatal
determinants of child growth, development and health. Pregnant women were recruited in two
French university hospitals (Nancy and Poitiers, 2003-2005) before 24 weeks of gestation. Exclusion
criteria were: multiple pregnancies, pre-pregnancy diabetes, illiteracy, and planned move outside the
region in the following 3 years. 2,002 women were initially included during pregnancy and 1,893
agreed to have their newborns take part in the study. Average age, proportion of unmarried couples,
and of children born with low birth weight in the EDEN study were comparable to national estimates,
but maternal educational level was somewhat higher [16]. Over the follow-up period, attrition rates
were highest in families in which the mother was young, had low educational level and low income,
did not live with the child’s father, smoked tobacco or had psychological difficulties in pregnancy, and
whose child did not have low birth weight.
4
Since study inception, there have been eight waves of data collection (pregnancy, the child’s birth, 4,
8, 12, 24, 36 months and 5 years). Data were collected by trained interviewers (pregnancy, birth, 36
months), by mothers’ and fathers’ self-reports at all study waves, and from medical records
(pregnancy, birth).
The EDEN cohort received approval from the Bicêtre Hospital ethics committee (CCPPRB) and
the Commission Nationale Informatique et Libertés (CNIL) overseeing ethical data collection in
France.
Measures
Maternal tobacco smoking
Mothers reported on their tobacco smoking before and during pregnancy on the initial EDEN study
questionnaire at 24-28 weeks of gestation (‘Did you smoke in the three months prior to pregnancy?’,
‘Did you smoke in the first trimester of pregnancy?’, ‘Do you smoke now, and if yes how many
cigarettes per day?’) and once the child was born (‘Did you smoke prior to pregnancy?’, ’Did you
smoke in the third trimester of pregnancy, and if yes how many cigarettes per day?’, ‘If you quit
smoking during pregnancy, when did you quit?’). Based on this information, we created a fourcategory variable assessing maternal tobacco use: non-smoker (reference category), quit smoking
prior to pregnancy, smoked in the first trimester of pregnancy (>=1 cigarette/day), smoked
throughout pregnancy (>=1 cigarette/day). In additional analyses, we divided the group of mothers
who quit smoking prior to pregnancy into two subgroups depending on whether they smoked during
follow-up.
Children’s socio-emotional development
Children’s socio-emotional development was ascertained using the Strengths and Difficulties
Questionnaire (SDQ) completed by the mothers when children were 5 years of age [17, 18]. This
validated instrument includes 25 items on 5 dimensions of children’s behaviour: emotional
symptoms, conduct problems, hyperactivity/inattention, peer relationship problems and prosocial
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behaviour. Each item is scored 0 (never), 1 (sometimes true) or 2 (certainly true) and items
composing each subscale are summed to generate a score ranging from 0 to 10. Following prior
research, children’s scores on all SDQ subscales were dichotomized at the 85th percentile, to study a
high, potentially clinically significant, level of symptoms [19].
Covariates
Covariates included were all potentially associated with children’s socio-emotional development:
characteristics of parental smoking, characteristics of children, mothers and families measured at
study baseline or longitudinally, that is combining all measures obtained across the eight waves of
EDEN study follow-up.
Parental smoking, other than maternal tobacco use before and during pregnancy, was ascertained
through maternal smoking post-pregnancy (yes vs. no), paternal smoking in pregnancy (yes vs. no),
and paternal smoking post-pregnancy (yes vs. no).
Children’s characteristics included the child’s sex (male vs. female), premature (<37 weeks gestation)
birth (yes vs. no), birth weight (<=2500 vs. >2500 g) ascertained from the child’s medical records, and
duration of breastfeeding (< 3 vs. >=3 months) ascertained from maternal reports up to the child’s 1st
birthday [20].
Maternal characteristics included age at the child’s birth (<30 vs. >=30 years), psychological
difficulties in pregnancy ascertained via high symptoms of depression measured with the CES-D
(score >=16)[21] and/or high anxiety measured with the STAI [22] (yes vs. no), maternal depression
post-pregnancy measured with the EPDS at 4, 8, and 12 months post-partum [23] and with the CES-D
at 36 months and 5 years [21] (yes vs. no), maternal alcohol use in pregnancy (>=1 vs. <1 glass of
alcohol/week).
Family characteristics included study center (Poitiers vs. Nancy), parents’ educational attainment
ascertained as highest of mother’s and father’s (< vs. >= any higher education), family income (<1500
vs. >=1500 euros/month, which corresponds to the lowest quartile of the distribution in our study
population [24]), parental separation between pregnancy and the age 5 assessment (yes vs. no),
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number of children in the family (>=1 vs. 0), and negative life events from pregnancy to the age 5
assessment : death of a close person, death of a child, home eviction, fire or other major damage to
the home, serious parental health problems, parental unemployment, legal problems, maternal
exposure to domestic or sexual violence (yes vs. no).
Statistical analysis
Our aim was to examine the association between maternal tobacco smoking in pregnancy and
children’s behavioural difficulties. Analyses were based on the complete study sample from
pregnancy to age 5 years (n=1,113). First, we conducted logistic regression analyses adjusted for
children’s sex and study centre. Second, to control for factors which covary with maternal smoking in
pregnancy and can bias the association with children’s behaviour, we calculated Inverse Probability
Weights (IPW) of exposure [25] based on all covariates potentially associated with our study outcome
[26]. This method renders study groups comparable on all measured covariates, thereby mimicking
the random allocation of exposure. Third, we conducted logistic regression analyses testing the
association between maternal tobacco smoking in pregnancy and children’s behaviour weighting the
analysis on IPWs. Fourth, we tested the association between the average number of cigarettes
smoked daily by the mother and children’s behaviour. Fifth, we tested for interactions with the child’s
sex, parental educational attainment and income level. Sixth, we calculated the fraction of cases of
high symptoms of hyperactivity/inattention potentially attributable to maternal smoking in
pregnancy, using the following formula: Attributable Fraction=[OR-1]/[n° exposed cases/n°cases][27].
All analyses were conducted using SAS 9.2 (Carey, NC).
Results
Characteristics of EDEN cohort children and families according to maternal tobacco use in pregnancy
are shown in Table 1. Overall, 7.8% of study mothers smoked only during the first trimester of
pregnancy and 12.9% throughout pregnancy. 30.5% of mothers smoked post-pregnancy, while 36.0%
of fathers smoked in pregnancy and 43.3% post-pregnancy. Factors associated with maternal tobacco
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use in pregnancy include maternal smoking post-pregnancy (p<0.0001), paternal smoking in
pregnancy (p<0.0001), paternal smoking post-pregnancy (p<0.0001), duration of breastfeeding
(p<0.0001), maternal age (p<0.0001), maternal psychological difficulties (p=0.0006), maternal
depression post-pregnancy (p=0.04), maternal alcohol use (p<0.0001), study center (p=0.0006),
parents’ educational attainment (p<0.0001), family income (p<0.0001), parental separation
(p=0.0003) and negative life events (p=0.0007).
Table 2 shows associations between maternal smoking in pregnancy and children’s behaviour
at age 5, controlling for children’s sex and study centre. Maternal smoking in pregnancy was only
associated with children’s symptoms of hyperactivity/inattention (tobacco smoking during the 1st
trimester of pregnancy: OR=1.95, 95% CI 1.13-3.38; tobacco smoking throughout pregnancy:
OR=2.11, 95% CI 1.36-3.27).
Table 3 shows associations between all potential covariates and children’s symptoms of
hyperactivity/inattention.
Table 4 shows IPW-controlled associations between maternal tobacco smoking in pregnancy
and children’s symptoms of hyperactivity/inattention. The OR associated with maternal smoking
during the 1st trimester of pregnancy was reduced compared to the sex and study center-adjusted
model and became statistically non-significant (OR=1.25, 95% CI 0.58-2.68). However, the OR
associated with maternal tobacco smoking throughout pregnancy was marginally higher and
remained statistically significant (OR=2.20, 95% CI 1.21-4.00).
In additional analyses, we observed a dose-response association between maternal tobacco
smoking and children’s levels of hyperactivity/inattention, however, due to a small sample size, the
ORs associated with different levels of maternal smoking were not statistically significant (1-9
cigarettes/ day: IPW-adjusted OR=1.49, 95% CI 0.52-4.21; >=10 cigarettes/ day: IPW-adjusted
OR=1.64, 0.53-4.64). The association between maternal smoking and children’s symptoms of
hyperactivity/ inattention did not vary with the child’s sex, parental educational attainment or family
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income. Overall, approximately 13% of cases of high symptoms of hyperactivity/inattention in
children were potentially attributable to maternal smoking in pregnancy.
Discussion
Our findings suggest that maternal smoking during pregnancy may specifically contribute to
symptoms of hyperactivity/inattention in children, which differs from the results of studies conducted
among siblings [10, 13] or among children born using assisted reproduction technologies [9].
However, these genetically-informative designs may suffer from bias due to participants’ selection
and the uneven distribution of confounders among the exposed and the non-exposed [14], thus the
jury is still out on the nature of the association between maternal tobacco use in pregnancy and
children’s behavior [28]. In the present study, we found a unique association between maternal
smoking in pregnancy and children’s behaviour, even after accounting for maternal smoking postpregnancy, paternal smoking and multiple characteristics of children and their families using the
propensity score technique which is more robust than traditional methods to control for covariates.
Our study contributes to research suggesting that maternal smoking during pregnancy may directly
influence the likelihood of symptoms of hyperactivity/inattention in the offspring.
Strengths and limitations
Key strengths of our study are: 1) a large size community based sample with prospective follow-up; 2)
repeated assessments of multiple characteristics of children and their families from pregnancy to age
5; 3) the use of propensity scores - a statistical method designed to account for confounding as well
as selection effects. Nevertheless, we also need to acknowledge limitations. First, families who did
not take part in the follow-up were more likely to experience socioeconomic difficulties, therefore the
relationship between maternal smoking in pregnancy and children’s behaviour may be
underestimated. Second, symptoms of hyperactivity/inattention were reported by children’s mothers
and could suffer from information bias [29]. Maternal reports of high levels of
hyperactivity/inattention are probably valid; nonetheless, future studies should aim to use multiple
9
sources of information (ex. mother, father or teacher, and child him/herself) [30] or study clinical
diagnoses of ADHD. Third, tobacco use in pregnancy was ascertained by the mothers and could be
underreported, which again would bias our results towards the null. Future studies should consider
ascertaining maternal tobacco use through questionnaires as well as biological measures. Fourth, we
did not assess potential confounders such as paternal psychopathology, use of substances other than
tobacco and genetic/biological factors; the inclusion of these elements in future investigations can
help disentangle the complex processes implicated in the etiology of hyperactivity/inattention.
Putative mechanisms
The association between maternal tobacco smoking in pregnancy and children’s symptoms of
hyperactivity/inattention may reflect several mechanisms. First, mothers who do not quit smoking in
pregnancy probably have especially high levels of nicotine dependence and can transmit this
heightened vulnerability to addiction and behavioral difficulties to their children [31]. We found no
association between paternal smoking and children’s behavior, which goes against the hypothesis of
genetic confounding, yet fathers are much less likely than mothers to reduce tobacco use before a
child’s birth and genetic factors may play a lesser role with regard to paternal than maternal smoking.
Second, maternal smoking in pregnancy may be a marker of environmental confounding by factors
such as maternal psychological difficulties related both to a decreased ability to quit smoking (despite
warnings and known fetus toxicity) and less positive parenting after the child’s birth. For example,
high levels of maternal smoking in pregnancy have been associated with mothers’ reduced feelings of
attachment towards the fetus [32] and worse mother–child attachment in infancy [33]. This lower
quality of mother-child attachment could in turn contribute to later ADHD symptoms [34]. A recent
review [35] reports that compared to persistent smokers, women who spontaneously quit during
pregnancy show a more secure pattern of attachment to their infant and higher levels of parenting
competence, implying that the ability to quit smoking may in part reflect the mother’s investment in
her pregnancy and child. Failure in quitting appears to be associated with maternal conduct disorder
but not ADHD, again going against the hypothesis that the association between maternal tobacco
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smoking and children’s symptoms of hyperactivity/inattention is solely due to genetic factors. Third,
maternal tobacco smoking may have direct teratological effects on fetal brain development in utero
and immediately after birth [36, 37]. These effects could occur through the impact of tobacco on
cerebral structures and connectivity, neurotransmission, as well as neuronal differentiation and
migration [37-39]. In addition, tobacco products and nicotine could impair placental function,
resulting in chronic fetal hypoxia and subsequent fetal growth retardation [40, 41]. Fourth, growing
evidence suggests that prenatal tobacco smoking may have epigenetic effects both on fetal and
placental tissues [42-44].
Implications
Tobacco smoking during pregnancy is one of the most common and preventable risk factors of poor
pregnancy and infant outcomes. Quitting smoking has many health benefits for the mother and her
child. Importantly, our findings suggest that smoking in the first trimester only is not associated with
children’s behavioral difficulties, underlining the potential benefits of smoking cessation during the
course of pregnancy. However, it is still possible that smoking during pregnancy is a marker of
biological or psychological risk which is transmitted intergenerationally. This implies that health
professionals should screen for these factors in women who do not quit smoking during pregnancy in
order to provide adequate support, potentially targeting characteristics such as insecure attachment,
parenting difficulties, maternal conduct disorder, or parental substance use disorders. Early action on
these characteristics could positively influence a range of outcomes in the offspring among which
symptoms of ADHD. As suggested by Massey et al. [35], among pregnant women who smoke tobacco,
efforts could be dedicated not only to smoking cessation but also to the development of psychoeducational and parenting interventions. We are not able to entirely reject the possibility that genetic
factors play a role in this association, either directly or via epigenetic processes, nonetheless,
maternal smoking in pregnancy may also have effects on children’s behavior, through physiological
mechanisms which are not yet fully uncovered. Future etiological research on the causes of ADHD,
11
should integrate measures of early environmental, biological, psychological and social processes
provided to the child by the mother and her surroundings.
Conclusions
Maternal tobacco smoking in pregnancy may contribute directly or through epigenetic mechanisms
to children’s symptoms of hyperactivity/inattention.
12
Funding and other support
The authors thank the EDEN study team for help in implementing the study. This work was supported
by: Fondation pour la Recherche Médicale (FRM); French Ministry of Research: IFR Program; INSERM
Human Nutrition National Research Program; Diabetes National Research Program (through a
collaboration with the French Association of Diabetic Patients (AFD)); French Ministry of Health;
French Agency for Environment Security (AFSSET); French National Institute for Population Health
Surveillance (InVS); Paris-Sud University; French National Institute for Health Education (INPES);
Nestlé; Mutuelle Générale de l'Education Nationale (MGEN); French speaking association for the
study of diabetes and metabolism (ALFEDIAM); National Agency for Research (ANR nonthematic
programme); and National Institute for Research in Public Health (IRESP: TGIR Cohorte Santé 2008
programme). Maria Melchior is the recipient of a Young Researcher Award from the French National
Research Agency (ANR). The founders had no further role in study design; in the collection, analysis
and interpretation of data; in the writing of the report; or in the decision to submit the paper for
publication.
Conflict of interest
The authors declare no conflicts of interest.
13
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(39) Heath CJ, King SL, Gotti C, Marks MJ, Picciotto MR. Cortico-thalamic connectivity is vulnerable
to nicotine exposure during early postnatal development through alpha4/beta2/alpha5
nicotinic acetylcholine receptors. Neuropsychopharmacol 2010;35:2324-38.
(40) Herrmann M, King K, Weitzman M. Prenatal tobacco smoke and postnatal secondhand smoke
exposure and child neurodevelopment. Current Opin Pediatrics 2008;20:184-90.
(41) Jauniaux E, Burton GJ. Morphological and biological effects of maternal exposure to tobacco
smoke on the feto-placental unit. Early Human Develop 2007;83:699-706.
(42) Suter M, Abramovici A, Aagaard-Tillery K. Genetic and epigenetic influences associated with
intrauterine growth restriction due to in utero tobacco exposure. Pediatr Endocrinol Rev
2010;8:94-102.
(43) Suter M, Ma J, Harris A, Patterson L, Brown KA, Shope C, et al. Maternal tobacco use
modestly alters correlated epigenome-wide placental DNA methylation and gene expression.
Epigenetics 2011;6:1284-94.
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and miR-146a in the placenta. Epigenetics 2010;5:583-9.
16
Table 1. Characteristics of mothers and children participating in the EDEN mother-child birth cohort
study according to maternal smoking in pregnancy (n=1113, %)
Maternal smoking in pregnancy
Parental tobacco smoking
Maternal smoking post pregnancy: No
Yes
Missing data n=11
Paternal smoking in pregnancy: No
Yes
Quit smoking Smoked during
Non-smoker
prior to
the 1st trimester
(n=777)
pregnancy
of pregnancy
(n=105)
(n=87)
91.7
31.4
29.1
8.3
68.6
70.9
p<0.0001
74.8
25.2
50.0
50.0
Missing data n=74
Paternal smoking post pregnancy: No
Yes
68.4
31.6
35.0
65.1
46.6
53.4
48.6
51.4
94.0
6.1
93.3
6.7
95.4
4.6
95.2
4.8
60.4
39.6
57.1
42.9
41.6
58.4
61.9
38.1
81.4
18.7
69.5
30.5
80.1
20.0
77.1
22.9
Missing data n=0
95.4
4.6
94.4
5.6
50.6
49.4
40.3
59.7
55.2
44.8
53.5
46.5
68.2
31.8
71.8
28.2
71.3
28.7
70.8
29.2
60.9
39.1
69.7
30.3
42.5
57.5
34.0
66.0
p=0.04
83.1
17.0
75.0
25.0
Missing data n=274
Family characteristics
Study centre: Nancy
Poitiers
95.8
4.2
p=0.0006
Missing data n=0
Maternal alcohol use in pregnancy: <1 glass/week
>=1 glass/week
97.7
2.3
p<0.0001
Missing data n=9
Maternal depression post pregnancy: No
Yes
47.9
52.1
p<0.0001
Missing data n=0
Maternal psychological difficulties in pregnancy: No
Yes
48.3
51.7
p=0.97
Missing data n=0
Maternal characteristics
Maternal age at child’s birth :<30 years
>=30 years
20.0
80.0
p=0.41
Missing data n=0
Duration of breastfeeding : >=3 months
< 3 months
37.2
62.8
p=0.97
Missing data n=0
Birthweight : >2500 g
<=2500 g
27.9
72.1
p<0.0001
Missing data n=0
Born premature : No
Yes
41.0
59.0
p<0.0001
Missing data n=14
Children’s characteristics
Sex : Female
Male
Smoked
throughout
pregnancy
(n=144)
3.5
96.5
p<0.0001
48.8
51.2
59.1
41.0
p=0.0006
17
Parents’ educational attainment : >=Higher education
< Higher education
72.5
27.5
69.9
30.1
Missing data n=8
Family income : >1500 euros/month
<=1500 euros/month
73.5
26.5
75.5
24.5
89.3
10.7
80.4
19.6
Missing data n=2
49.3
50.7
80.0
20.0
78.6
21.4
54.0
46.0
53.5
46.5
39.1
60.9
27.5
72.5
p=0.0003
45.2
54.8
54.3
45.7
Missing data n=0
Negative life events: No
Yes
63.5
36.5
p<0.0001
Missing data n=19
Number of siblings: None
>=1
46.1
53.9
p<0.0001
Missing data n=13
Parental separation: No
Yes
62.1
37.9
p=0.07
45.7
54.3
44.8
55.2
p=0.0007
18
Table 2. Maternal tobacco smoking in pregnancy and children’s emotional and behavioral symptoms at age 5 years (EDEN mother-child birth cohort study,
n=1113, logistic regression models adjusted for children’s sex and study center, OR, 95% CI)
High emotional
High conduct problems High symptoms of
High peer relationship
Low prosocial
symptoms
(174/1112)
hyperactivity/
problems
behavior
(238/1113)
Inattention
(160/1112)
(365/1110)
(176/1113)
Maternal tobacco smoking in pregnancy
Non-smoker (n=777)
1
1
1
1
1
Quit smoking prior to pregnancy (n=105)
1.05 (0.63-1.73)
0.95 (0.53-1.70)
1.35 (0.76-2.37)
1.13 (0.64-2.00)
0.86 (0.55-1.34)
Smoked in the 1st trimester of pregnancy (n=87)
1.41 (0.85-2.34)
1.36 (0.76-2.43)
1.95 (1.13-3.38)
1.33 (0.73-2.41)
0.98 (0.61-1.58)
Smoked throughout pregnancy (n=144)
1.25 (0.82-1.90)
1.56 (0.99-2.48)
2.11 (1.36-3.27)
1.22 (0.75-2.00)
0.77 (0.52-1.15)
Table 3. Characteristics of mothers and children participating in the EDEN mother-child birth cohort
study in relation to high symptoms of hyperactivity/inattention (n=1113, OR, 95% CI)
Parental tobacco smoking
Maternal tobacco smoking post pregnancy: No
Yes
Paternal tobacco smoking in pregnancy: No
Yes
Not known
Paternal tobacco smoking post pregnancy: No
Yes
Children’s characteristics
Sex : Female
Male
Born premature : No
Yes
Birthweight : >2500 g
<=2500 g
Duration of breastfeeding : >=3 months
< 3 months
Maternal characteristics
Maternal age at child’s birth :<30 years
>=30 years
Maternal psychological difficulties in pregnancy: No
Yes
Maternal depression post pregnancy: No
Yes
Maternal alcohol use in pregnancy: <1 glass/week
>=1 glass/week
No information
Family characteristics
Study center: Nancy
Poitiers
Parents’ educational attainment : >=Higher education
< Higher education
Family income : >1500 euros/month
<=1500 euros/month
Parental separation: No
Yes
Number of siblings: None
>=1
Negative life events: No
Yes
N
ORs, 95% CI , p-value
1102
1
1.68 (1.20-2.34)
1
1.28 (0.68-2.42)
1.33 (0.95-1.88)
1
1.17 (0.84-1.62)
1113
1099
1113
1113
1113
1113
1113
1104
1113
1113
1113
1105
1100
1094
1113
1111
1
1.95 (1.39-2.74)
1
1.03 (0.51-2.06)
1
1.09 (0.52-2.28)
1
1.67 (1.21-2.30)
1
0.60 (0.43-0.83)
1
1.69 (1.18-2.42)
1
1.84 (1.29-2.62)
1
1.25 (0.81-1.93)
1.00 (0.68-1.48)
1
1.66 (1.19-2.32)
1
2.06 (1.48-2.86)
1
2.29 (1.64-3.20)
1
1.59 (1.03-2.44)
1
0.65 (0.47-0.90)
1
1.62 (1.15-2.28)
Table 4. Maternal tobacco smoking in pregnancy and children’s high symptoms of
hyperactivity/inattention at age 5 years (EDEN mother-child birth cohort study, n=997, Inverse
probability weights-controlled ORs, 95% CI)a
High symptoms of
hyperactivity/
inattention
Maternal tobacco smoking in pregnancy
Non-smoker (103/777)
Quit smoking prior to pregnancy (17/105)
Smoked during the 1st trimester of pregnancy (20/87)
Smoked throughout pregnancy (36/144)
a
1
1.19 (0.41-3.48)
1.06 (0.51-2.21)
2.20 (1.21-4.00)
Multivariate analyses are controlled for inverse probability weights (IPW) based on children’s sex, premature
birth, birth weight, duration of breastfeeding, maternal age at birth, maternal psychological difficulties in
pregnancy, maternal depression post-pregnancy, maternal alcohol use in pregnancy, maternal smoking post
pregnancy, paternal tobacco smoking during and post pregnancy, study center, parents’ educational attainment,
family income, parental separation, number of siblings, negative life events.

Maternal tobacco smoking in pregnancy and

Transcription

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